Alzheimer's Disease is a devastating illness affecting nearly 4 million Americans, costing the country billions of dollars in direct care, lost income, and—most importantly—costing untold anguish for millions of American families.
The disease symptoms start insidiously, with relatively non-specific signs and symptoms. Subtle memory loss, occasional word-finding difficulties, irritability and aggressiveness can all be signs of a disease process from a clinical perspective, that has already affected the brain substantially. Over the course of several years, the disease progresses to profound amnesia to the point where patients do not know themselves, or their family. Frequently this amnesia is accompanied by frustration and paranoia. Ultimately patients lose all ability to care for themselves—to dress themselves, to bathe, even to control their bowel and bladder. Their last years are frequently spent in a nursing home. As the average age of the population grows, the number of Alzheimer patients will explode because it is a strongly age-related illness.
While these clinical symptoms are going on, the changes in the brain are marked. By the time the very first clinical symptoms appear, there are innumerable microscopic deposits of a protein called amyloid (“A-beta” or “Aβ”), as well as changes in the brain cells themselves. As the disease progresses, the brain shrinks and losses as many as 50% of its cells.
Genetic risk factor analysis and molecular biology suggest strongly that it is the depositon of Aβ that is the critical aspect of this disease process. Seeing Aβ and neuronal change, neurofibrillary tangles, in the brain under the microscope provides a definitive diagnosis to a neuropathologist. However, these changes are far too small (100 times too small) to be seen by even the most sophisticated clinical imaging devices such as computerized tomography or magnetic resonance imaging.
The ability to detect amyloid deposition and neurofibrillary changes in neurons in vivo would provide a definitive diagnostic test for Alzheimer's Disease, and compares to quite non-specific clinical symptoms at the beginning of the disease process. Moreover, the ability to visualize and quantitate these changes would provide a definitive means of tracking progression of disease, and effectiveness of potential therapeutics.
The present invention is directed to overcoming the deficiencies in the prior art by providing a method of diagnostically detecting and imaging Alzheimer's Disease and other neurodegenerative diseases.